2H-phthalazin-1-one derivatives and drug containing its derivatives as active ingredient

Abstract

Poly(ADP-ribose)polymerase inhibitors containing as the active ingredient 2H-phthalazin-1-one derivatives represented by general formula (I) (wherein each symbol is as defined in the description) or salts thereof. The compounds of the general formula (I) inhibit poly(ADP-ribose)polymerase and are useful as preventives and/or remedies for various ischemic diseases (brain, heart, digestive tract, skeletal muscle, retina, etc.), inflammatory diseases (inflammatory intestinal diseases, multiple encephalosclerosis, arthritis, etc.), nerve degeneration diseases (extrapyramidal disorder, Alzheimer's disease, muscular dystrophy, etc.), diabetes, shock, head trauma, renal insufficiency, hyperalgesia, etc. These compounds are also useful as sensitizers for agents against retroviruses (HIV, etc.) and chemotherapy for cancer.

What is claimed is:  
     
       1. A method for preventing and/or treating diseases induced by poly(ADP-ribose)polymerase, which comprises administering to a subject in need thereof an effective amount of a compound of formula (I)                    
       wherein R 1  is  
       (i) C1-4 alkyl substituted by hydroxy or amino, or  
       (ii)—A 1 —A 2 —A 3 ,  
       in which A 1  is  
       (i)—NR 3 C(O)—,  
       (ii)—NR 4 C(S)—,  
       (iii)—NR 5 SO 2 —,  
       (iv)—CH 2 —NR 6 —,  
       (v)—CH 2 —O—,  
       (vi)—OC(O)—,  
       (vii)—CH 2 —NR 7 C(O)—,  
       (viii)—NR 8 C(O)NR 9 —,  
       (ix)—NR 10 C(O)O—,  
       (x)—NR 11 C(S)NR 12 ,  
       (xi)—N(R 13 )—, or                    
       with the proviso that the linkage of the right side of each group represented by A 1  binds to A 2 ,  
       wherein R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14  and R 15  each, independently, is a hydrogen atom, C1-4 alkyl, phenyl or C1-4 alkyl substituted by phenyl,  
       A 2  is  
       (i) C1-8 alkylene,  
       (ii) C2-8 alkenylene,  
       (iii) Cyc 1 ,  
       (iv)—(C1-4 alkylene)—O—(C1-4 alkylene)—,  
       (v)—(C1-4 alkylene)—S—(C1-4 alkylene)—,  
       (vi)—(C1-4 alkylene)—NR 16 —(C1-4 alkylene)—,  
       (vii)—(Cyc 1 )—(C1-8 alkylene)—,  
       (viii)—(C1-8 alkylene)—(Cyc 1 )—, or  
       (ix)—(C1-4 alkylene)—(Cyc 1 )—(C1-4 alkylene),  
       R 16  is a hydrogen atom, C1-8 alkyl, C1-8 alkoxycarbonyl, phenyl or C1-8 alkyl substituted by phenyl,  
       Cyc 1  is  
       (i) a 3-10 membered mono-cyclic or bi-cyclic carbocyclic ring, or  
       (ii) a 3-10 membered mono-cyclic or bi-cyclic hetero ring having 1-4 nitrogen atoms, 1-2 oxygen atoms and/or one sulfur atom,  
       A 3  is  
       (i) a hydrogen atom,  
       (ii)—NR 17 R 18 ,  
       (iii) Cyc 2 ,  
       (iv)—OR 19 ,  
       (v)—COOR 20 ,  
       (vi)—CONR 21 R 22 ,  
       (vii) C≡N,  
       (viii) a halogen atom,                    
       R 17 , R 21  and R 22  each, independently, is  
       (i) a hydrogen atom,  
       (ii) C1-8 alkyl,  
       (iii) C2-8 alkenyl,  
       (iv) C2-8 alkynyl,  
       (v) Cyc 3 ,  
       (vi) C1-8 alkoxy,  
       (vii) C2-8 alkenyloxy,  
       (viii) C2-8 alkynyloxy, or  
       (ix) C1-8 alkyl substituted by Cyc 3 , C1-8 alkoxy, C1-8 alkylthio, C≡N, hydroxy or 1-3 of halogen atom,  
       R 18  is  
       (i) a hydrogen atom,  
       (ii) C1-8 alkyl,  
       (iii) C2-8 alkenyl,  
       (iv) C2-8 alkynyl,  
       (v) C1-8 alkoxycarbonyl,  
       (vi) C2-8 acyl,  
       (vii) C3-8 cycloalkyl,  
       (viii) C1-8 alkoxycarbonyl substituted by Cyc 3  or 1-3 of halogen atom, or  
       (ix) C1-8 alkyl substituted by C1-8 alkoxy,  
       R 19  and R 20  each, independently, is a hydrogen atom or C1-8 alkyl,  
       R 23 , R 24 , R 25 , R 26 , R 27 , R 28  and R 29  each, independently, is a hydrogen atom, C1-4 alkyl, C1-8 alkoxycarbonyl, phenyl, or C1-4 alkyl substituted by phenyl,  
       Cyc 2  is a 3-10 membered mono-cyclic or bi-cyclic hetero ring having 1-4 nitrogen atoms, 1-2 oxygen atoms and/or one sulfur atom,  
       Cyc 3  is  
       (i) a 3-10 membered mono-cyclic or bi-cyclic carbocyclic ring, or  
       (ii) a 3-10 membered mono-cyclic or bi-cyclic hetero ring having 1-4 nitrogen atoms, 1-2 oxygen atoms and/or one sulfur atom,  
       the above-mentioned Cyc 1 , Cyc 2  and Cyc 3  each, independently, may be optionally substituted by 1-3 of substituents selected from the following (i)-(vii):  
       (i) C1-8 alkyl,  
       (ii) C2-8 alkenyl,  
       (iii) C2-8 alkynyl,  
       (iv) C1-8 alkoxy,  
       (v) C1-8 alkoxycarbonyl,  
       (vi) oxo, and  
       (vii) C1-8 alkyl substituted by C1-8 alkoxy;  
       R 2  is a hydrogen atom, a halogen atom, nitro, hydroxy, —NR 30 R 31 , C1-8 alkyl, C1-8 alkoxy, or C1-8 alkyl or C1-8 alkoxy substituted by 1-3 of halogen atoms,  
       R 30  and R 31  each, independently, is a hydrogen atom, C1-4 alkyl, C1-8 alkoxycarbonyl, phenyl, C1-4 alkyl substituted by phenyl,  
       with the proviso that, R 1  is not dimethylamino,  
       or a non-toxic salt thereof and a carrier. 
     
     
       2. A 2H-phthalazin-1-one derivative of the formula (Ia)                    
       wherein R 1a  is  
       (i) C1-4 alkyl substituted by hydroxy or amino, or  
       (ii) A 1a —A 2a —A 3a ,  
       in which A 1a  is  
       (i)—NR 3a C(O)—,  
       (ii) NR 4a C(S)—,  
       (iii)—NR 5a SO 2 —,  
       (iv)—CH 2 —NR 6a —,  
       (v)—CH 2 —O—,  
       (vi)—OC(O)—,  
       (vii)—CH 2 —NR 7a C(O)—,  
       (viii) NR 8a C(O)NR 9a —,  
       (ix)—NR 10a C(O)O—,  
       (x)—NR 11a C(S)NR 12a —,  
       (xi)—NR( 13a )—, or                    
       with the proviso that the linkage of the right side of each group represented by A 1a  binds to A 2a ,  
       wherein R 3a , R 4a , R 5a , R 6a , R 7a , R 8a , R 9a , R 10a , R 11a , R 12a , R 13a , R 14a  and R 15a  each, independently, is a hydrogen atom, C1-4 alkyl, phenyl or C1-4 alkyl substituted by phenyl,  
       A 2a  is  
       (i) C1-8 alkylene,  
       (ii) C2-8 alkenylene,  
       (iii) Cyc 1a ,  
       (iv)—(C1-4 alkylene)—O—(C1-4 alkylene)—,  
       (v)—(C1-4 alkylene)—S—(C1-4 alkylene)—,  
       (vi)—(C1-4 alkylene)—NR 16a (C1-4 alkylene)—,  
       (vii)—(Cyc 1a )—(C1-8 alkylene)—,  
       (viii)—(C1-8 alkylene)—(Cyc 1a )—, or  
       (ix)—(C1-4 alkylene)—(Cyc 1a )—(C1-4 alkylene),  
       R 16a  is a hydrogen atom, C1-8 alkyl, C1-8 alkoxycarbonyl, phenyl or C1-8 alkyl substituted by phenyl,  
       Cyc 1a  is  
       (i) a 3-10 membered mono-cyclic or bi-cyclic carbocyclic ring, or  
       (ii) a 3-10 membered mono-cyclic or bi-cyclic hetero ring having 1-4 nitrogen atoms, 1-2 oxygen atoms and/or one sulfur atom,  
       A 3a  is  
       (i) a hydrogen atom,  
       (ii)—N 17a R 18a ,  
       (iii) Cyc 2a ,  
       (iv) OR 19a ,  
       (v)—COOR 20a ,  
       (vi)—CONR 21a R 22a ,  
       (vii) C≡N,  
       (viii) a halogen atom,                    
       R 17a , R 21a  and R 22a  each, independently, is  
       (i) a hydrogen atom,  
       (ii) C1-8 alkyl,  
       (iii) C2-8 alkenyl,  
       (iv) C2-8 alkynyl,  
       (v) Cyc 3a ,  
       (vi) C1-8 alkoxy,  
       (vii) C2-8 alkenyloxy,  
       (viii) C2-8 alkynyloxy, or  
       (ix) C1-8 alkyl substituted by Cyc 3a , C1-8 alkoxy, C1-8 alkylthio, C≡N, hydroxy or 1-3 of halogen atom,  
       R 18a  is  
       (i) a hydrogen atom,  
       (ii) C1-8 alkyl,  
       (iii) C2-8 alkenyl,  
       (iv) C2-8 alkynyl,  
       (v) C1-8 alkoxycarbonyl,  
       (vi) C2-8 acyl,  
       (vii) C3-8 cycloalkyl,  
       (viii) C1-8 alkoxycarbonyl substituted by Cyc 3a  or 1-3 of halogen atom, or  
       (ix) C1-8 alkyl substituted by C1-8 alkoxy,  
       R 19a  and R 20  each, independently, is a hydrogen atom or C1-8 alkyl,  
       R 23a , R 24a , R 25a , R 26a , R 27a , R 28a  and R 29a  each independently, is a hydrogen atom, C1-4 alkyl, C1-8 alkoxycarbonyl, phenyl, or C1-4 alkyl substituted by phenyl,  
       Cyc 2a  is a 3-10 membered mono-cyclic or bi-cyclic hetero ring having 1-4 nitrogen atoms, 1-2 oxygen atoms and/or one sulfur atom,  
       Cyc 3a  is  
       (i) a 3-10 membered mono-cyclic or bi-cyclic carbocyclic ring, or  
       (ii) a 3-10 membered mono-cyclic or bi-cyclic hetero ring having 1-4 nitrogen atoms, 1-2 oxygen atoms and/or one sulfur atom,  
       the above-mentioned Cyc 1a , Cyc 2a  and Cyc 3a  each, independently, may be optionally substituted by 1-3 of substituents selected from the following (i)-(vii):  
       (i) C1-8 alkyl,  
       (ii) C2-8 alkenyl,  
       (iii) C2-8 alkynyl,  
       (iv) C1-8 alkoxy,  
       (v) C1-8 alkoxycarbonyl,  
       (vi) oxo, and  
       (vii) C1-8 alkyl substituted by C1-8 alkoxy;  
       R 2a  is a hydrogen atom, a halogen atom, nitro, hydroxy, —NR 30a R 31a , C1-8 alkyl, C1-8 alkoxy, or C1-8 alkyl or C1-8 alkoxy substituted by 1-3 of halogen atoms,  
       R 30a  and R 31a each, independently, is a hydrogen atom, C1-4 alkyl, C1-8 alkoxycarbonyl, phenyl, C1-4 alkyl substituted by phenyl,  
       with the proviso that, R 1a  is not dimethylamino and the compound is not 4-(2-acetyloxyphenyl)-2H-phthalazin-1-one,  
       or a non-toxic salt thereof. 
     
     
       3. A compound according to  claim 2 , 
       in which 
       R 16a  is a hydrogen atom, C1-4 alkyl, C1-8 alkoxycarbonyl, phenyl, or C1-4 alkyl substituted by phenyl,  
       Cyc 1a  is  
       (i) a 3-10 membered mono-cyclic or bi-cyclic carbocyclic ring, or  
       (ii) a 3-10 membered mono-cyclic or bi-cyclic hetero ring having 1-4 nitrogen atoms, one oxygen atoms and/or one sulfur atom, and Cyc 1a  may be substituted by C1-8 alkoxycarbonyl,  
       A 3a  is  
       (i) a hydrogen atom,  
       (ii)—N 17a R 18a ,  
       (iii) Cyc 2a ,  
       (iv)—OR 19a ,  
       (v)—COOR 20a ,  
       (vi)—CONR 21a R 22a ,                    
       R 17a , R 21a  and R 22a  each, independently, is a hydrogen atom, C1-4 alkyl, phenyl, or C1-4 alkyl substituted by phenyl,  
       R 18a  is a hydrogen atom, C1-4 alkyl, C1-8 alkoxycarbonyl, C2-5 acyl, or C1-4 alkoxycarbonyl substituted by phenyl,  
       R 19a  and R 20a  each, independently, is a hydrogen atom or C1-4 alkyl,  
       Cyc 2a  is a 3-10 membered mono-cyclic or bi-cyclic hetero ring having 1-4 nitrogen atoms, one oxygen atoms and/or one sulfur atom, substituted by C1-8 alkoxycarbonyl,  
       R 2a  is a hydrogen atom, a halogen atom, nitro, or NR 30a R 31a .  
     
     
       4. A compound according to  claim 2 , wherein 
       R 1a  is —A 1a —A 2a —A 3a ,  
       A 1a  and A 2a  is the same meaning as  claim 2  defined,  
       A 3a  is (ii)—NR 17a R 16a , (iii) Cyc 2a , (vii)—C≡N, or (viii) a halogen atom, with the proviso that, when A 3a  is NR 17a R 18a , then R 17a  represents the groups except a hydrogen atom, C1-4 alkyl, phenyl, or C1-4 alkyl substituted by phenyl, Cyc 2a  is a 3-10 membered mono-cyclic or bi-cyclic hetero ring containing 1-4 nitrogen atoms, 1-2 oxygen atoms and/or one sulfur atom, substituted by 1-3 of substituent selected from C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, oxo, or C1-8 alkyl substituted by C1-8 alkoxy (with the proviso that when the substituent is selected from C1-8 alkyl, C1-8 alkoxy, or C1-8 alkyl substituted by C1-8 alkoxy, then the number of the substituent is 2 or 3).  
     
     
       5. A compound according to  claim 2 , 
       wherein  
       R 2a  is hydroxy, C1-8 alkyl, C1-8 alkoxy, or  
       C1-8 alkyl or C1-8 alkoxy substituted by 1-3 of halogen.  
     
     
       6. A compound according to  claim 2 , 
       wherein R 1a  is —A 1a —A 2a —A 3a  and  
       A 1a  is —NR 3a C(O)—.  
     
     
       7. A compound according to  claim 2 , which is 
       (1) 4-(3-(Hydroxymethyl)phenyl)-2H-phthalazin-1-one,  
       (2) 4-(3-(Aminomethyl)phenyl)-2H-phthalazin-1-one,  
       (3) 4-(3-(Dimethylaminomethyl)phenyl)-2H-phthalazin-1-one,  
       (4) 4-(3-(5-(t-Butoxycarbonylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (5) 4-(3-(2-(t-Butoxycarbonylamino)acetylamino)phenyl)-2H-phthalazin-1-one,  
       (6) 4-(3-(4-(Benzyloxycarbonylamino)butyrylamino)phenyl)-2H-phthalazin-1-one,  
       (7) 4-(3-(6-(t-Butoxycarbonylamino)hexanoylamino)phenyl)-2H-phthalazin-1-one,  
       (8) 4-(3-(3-(Benzyloxycarbonylamino)propionylamino)phenyl)-2H-phthalazin-1-one,  
       (9) 4-(3-(2-(t-Butoxycarbonylamino)acetylaminomethyl)phenyl)-2H-phthalazin-1-one,  
       (10) 4-(3-(3-(t-Butoxycarbonylamino)propionylaminomethyl)phenyl)-2H-phthalazin-1-one,  
       (11) 4-(3-(1-t-Butoxycarbonylpiperidin-4-ylcarbonylamino)phenyl)-2H-phthalazin-1-one,  
       (12) 4-(3-(4-(t-Butoxycarbonylamino)butyrylaminomethyl)phenyl)-2H-phthalazin-1-one,  
       (13) 4-(3-(5-(t-Butoxycarbonylamino)valerylaminomethyl)phenyl)-2H-phthalazin-1-one,  
       (14) 4-(2-(5-(t-Butoxycarbonylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (15) 4-(3-(3-(Indol-3-yl)propionylamino)phenyl)-2H-phthalazin-1-one,  
       (16) 4-(3-(5-(Morpholin-4-yl)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (17) 4-(3-(2-(Pyridin-4-yl)acetylamino)phenyl)-2H-phthalazin-1-one,  
       (18) 4-(3-(5-(Pyrrolidin-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (19) 4-(3-(5-(Dimethylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (20) 4-(3-(3-(Pyridin-3-yl)propionylamino)phenyl)-2H-phthalazin-1-one,  
       (21) 4-(3-(5-(N-Methyl-N-t-butoxycarbonylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (22) 4-(3-(2-(2-(t-Butoxycarbonylamino)ethylthio)acetylamino)phenyl)-2H-phthalazin-1-one,  
       (23) 4-(3-(2-(N-(2-(t-Butoxycarbonylamino)ethyl)-N-t-butoxycarbonylamino)acetylamino)phenyl)-2H-phthalazin-1-one,  
       (24) 4-(3-(5-(t-Butoxycarbonylamino)valeryloxy)phenyl)-2H-phthalazin-1-one,  
       (25) 4-(3-(2-(3-(t-Butoxycarbonylamino)phenyl)acetylamino)phenyl)-2H-phthalazin-1-one,  
       (26) 4-(3-(3-(t-Butoxycarbonylaminomethyl)benzoylamino)phenyl)-2H-phthalazin-1-one,  
       (27) 4-(3-(trans-4-(t-Butoxycarbonylaminomethyl)cyclohexylcarbonylamino)phenyl)-2H-phthalazin-1-one,  
       (28) 4-(3-(4-(t-Butoxycarbonylamino)cyclohexylcarbonylamino)phenyl)-2H-phthalazin-1-one,  
       (29) 4-(3-(4-(t-Butoxycarbonylaminomethyl)benzoylamino)phenyl)-2H-phthalazin-1-one,  
       (30) 4-(3-(2-(4-(t-Butoxycarbonylamino)phenyl)acetylamino)phenyl)-2H-phthalazin-1-one,  
       (31) 4-(3-((E)-3-(1-(t-Butoxycarbonyl)imidazol-4-yl)propenoylamino)phenyl)-2H-phthalazin-1-one,  
       (32) 4-(3-(5-Aminovalerylamino)phenyl)-2H-phthalazin-1-one,  
       (33) 4-(3-(2-Aminoacetylamino)phenyl)-2H-phthalazin-1-one,  
       (34) 4-(3-(6-Aminohexanoylamino)phenyl)-2H-phthalazin-1-one,  
       (35) 4-(3-(2-Aminoacetylaminomethyl)phenyl)-2H-phthalazin-1-one,  
       (36) 4-(3-(3-Aminopropionylaminomethyl)phenyl)-2H-phthalazin-1-one,  
       (37) 4-(3-(Piperidin-4-ylcarbonylamino)phenyl)-2H-phthalazin-1-one,  
       (38) 4-(3-(4-Aminobutyrylaminomethyl)phenyl)-2H-phthalazin-1-one,  
       (39) 4-(3-(5-Aminovalerylaminomethyl)phenyl)-2H-phthalazin-1-one,  
       (40) 4-(2-(5-Aminovalerylamino)phenyl)-2H-phthalazin-1-one,  
       (41) 4-(3-(5-(Methylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (42) 4-(3-(2-(2-Aminoethylthio)acetylamino)phenyl)-2H-phthalazin-1-one,  
       (43) 4-(3-(2-(2-Aminoethylamino)acetylamino)phenyl)-2H-phthalazin-1-one,  
       (44) 4-(3-(5-Aminovaleryloxy)phenyl)-2H-phthalazin-1-one,  
       (45) 4-(3-(2-(3-Aminophenyl)acetylamino)phenyl)-2H-phthalazin-1-one,  
       (46) 4-(3-(3-(Aminomethyl)benzoylamino)phenyl)-2H-phthalazin-1-one,  
       (47) 4-(3-(trans-4-(Aminomethyl)cyclohexylcarbonylamino)phenyl)-2H-phthalazin-1-one,  
       (48) 4-(3-(4-Aminocyclohexylcarbonylamino)phenyl)-2H-phthalazin-1-one,  
       (49) 4-(3-(4-(Aminomethyl)benzoylamino)phenyl)-2H-phthalazin-1-one,  
       (50) 4-(3-(2-(4-Aminophenyl)acetylamino)phenyl)-2H-phthalazin-1-one,  
       (51) 4-(3-((E)-3-(Imidazol-4-yl)propenoylamino)phenyl)-2H-phthalazin-1-one,  
       (52) 4-(3-(Acetylamino)phenyl)-2H-phthalazin-1-one,  
       (53) 4-(3-(Hexanoylamino)phenyl)-2H-phthalazin-1-one,  
       (54) 4-(3-(Benzoylamino)phenyl)-2H-phthalazin-1-one,  
       (55) 4-(3-(Butyrylamino)phenyl)-2H-phthalazin-1-one,  
       (56) 4-(3-(Valerylamino)phenyl)-2H-phthalazin-1-one,  
       (57) 4-(3-(Mesylamino)phenyl)-2H-phthalazin-1-one,  
       (58) 4-(3-(Butylsulfonylamino)phenyl)-2H-phthalazin-1-one,  
       (59) 4-(2-(Acetylamino)phenyl)-2H-phthalazin-1-one,  
       (60) 4-(4-Chloro-3-(acetylamino)phenyl)-2H-phthalazin-1-one,  
       (61) 4-(3-(4-(Methoxycarbonyl)butyrylamino)phenyl)-2H-phthalazin-1-one,  
       (62) 4-(3-(Acetoxy)phenyl)-2H-phthalazin-1-one,  
       (63) 4-(3-(4-Aminobutyrylamino)phenyl)-2H-phthalazin-1-one,  
       (64) 4-(3-(3-Aminopropionylamino)phenyl)-2H-phthalazin-1-one,  
       (65) 4-(3-(4-Carboxybutyrylamino)phenyl)-2H-phthalazin-1-one,  
       (66) 4-(3-(5-Hydroxyvalerylamino)phenyl)-2H-phthalazin-1-one,  
       (67) 4-(3-(4-(t-Butoxycarbonylamino)butylaminomethyl)phenyl)-2H-phthalazin-1-one,  
       (68) 4-(3-(4-Aminobutylaminomethyl)phenyl)-2H-phthalazin-1-one,  
       (69) 4-(3-(3-Ethyl-2-thioureido)phenyl)-2H-phthalazin-1-one,  
       (70) 4-(3-(3-Ethylureido)phenyl)-2H-phthalazin-1-one,  
       (71) 4-(3-(Ethoxycarbonylamino)phenyl)-2H-phthalazin-1-one,  
       (72) 4-(3-(5-(t-Butoxycarbonylamino)pentylamino)phenyl)-2H-phthalazin-1-one,  
       (73) 4-(3-(5-Aminopentylamino)phenyl)-2H-phthalazin-1-one,  
       (74) 4-(3-(Propylthiocarbonylamino)phenyl)-2H-phthalazin-1-one,  
       (75) 4-(3-(5-(Acetylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (76) 4-(3-(3-(3-t-Butoxycarbonylaminopropyl)-2-thioureido)phenyl)-2H-phthalazin-1-one,  
       (77) 4-(3-(3-(3-Aminopropyl)-2-thioureido)phenyl)-2H-phthalazin-1-one,  
       (78) 4-(3-(6-Dimethylaminohexanoylamino)phenyl)-2H-phthalazin-1-one,  
       (79) 4-(3-(5-(Thiazolidin-3-yl)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (80) 4-(3-(5-(Furan-2-ylmethylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (81) 4-(3-(5-(N-Methyl-N-propylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (82) 4-(3-(5-(2-Dimethylaminoethylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (83) 4-(3-(5-Diethylaminovalerylamino)phenyl)-2H-phthalazin-1-one,  
       (84) 4-(3-(5-(Azetidine-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (85) 4-(3-(5-Benzylaminovalerylamino)phenyl)-2H-phthalazin-1-one,  
       (86) 4-(3-(5-(N-(Furan-2-yl)methyl-N-methylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (87) 4-(3-(5-(N-t-Butyl-N-methylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (88) 4-(3-(5-(N-Isobutyl-N-methylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (89) 4-(3-(4-Morpholinobutyrylamino)phenyl)-2H-phthalazin-1-one,  
       (90) 4-(3-(5-(N-Ethyl-N-methylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (91) 4-(3-(5-(Thiophen-2-ylmethylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (92) 4-(3-(5-(N-Methyl-N-isopropylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (93) 4-(3-(5-(Tetrahydrofuran-2-ylmethylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (94) 4-(3-(5-t-Butylaminovalerylamino)phenyl)-2H-phthalazin-1-one,  
       (95) 4-(3-(5-sec-Butylaminovalerylamino)phenyl)-2H-phthalazin-1-one,  
       (96) 4-(3-(5-Ethylaminovalerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,  
       (97) 4-(3-(5-Butylaminovalerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,  
       (98) 4-(3-(5-Morpholinovalerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,  
       (99) 4-(3-(5-Thiomorpholinovalerylamino)phenyl)-2H-phthalazin-1-one,  
       (100) 4-(3-(5-(4-Methylpiperazin-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (101) 4-(3-(5-Dimethylaminovalerylamino)4-fluorophenyl)-2H-phthalazin-1-one,  
       (102) 4-(3-(5-(N-Methyl-N-propylamino)valerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,  
       (103) 4-(3-(5-Isobutylaminovalerylamino)phenyl)-2H-phthalazin-1-one,  
       (104) 4-(3-(5-(Piperidin-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (105) 4-(3-(5-(Perhydroazepin-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (106) 4-(3-(5-(N-Ethyl-N-2-methoxyethylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (107) 4-(3-(5-Morpholinovalerylamino)-4-fluorophenyl)-2H-phthalazin-1-one,  
       (108) 4-(3-(5-(1,2,5,6-Tetrahydropyridin-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (109) 4-(3-(5-(Pyrrolidin-1-yl)valerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,  
       (110) 4-(3-(5-((2S)-2-Methoxymethylpyrrolidin-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (111) 4-(3-(5-(1,2,3-Triazol-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (112) 4-(3-(5-(N-2-Methoxyethyl-N-methylamino)valerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,  
       (113) 4-(3-(5-(Imidazol-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (114) 4-(3-(5-(3-Methoxypyrrolidin-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (115) 4-(3-(5-(3-Methoxypiperidin-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (116) 4-(3-(5-((2R)2-Methoxymethylpyrrolidin-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (117) 4-(3-(5-(4-Methoxypiperidin-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (118) 4-(3-(5-Isobutylaminovalerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,  
       (119) 4-(3-(5-(Pyrrolidin-1-yl)valerylamino)-4-fluorophenyl)-2H-phthalazin-1-one,  
       (120) 4-(3-(6-Morpholinohexanoylamino)phenyl)-2H-phthalazin-1-one,  
       (121) 4-(3-(5-(Perhydroazepin-1-yl)valerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,  
       (122) 4-(3-(5-(2-Hydroxyethylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (123) 4-(3-(5-(3-Methoxypiperidin-1-yl)valerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,  
       (124) 4-(3-(5-((3R)-3-Methoxypiperidin-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (125) 4-(3-(5-((3S)-3-Methoxypiperidin-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (126) 4-(3-(5-(3-Methoxypiperidin-1-yl)valerylamino)-4-fluorophenyl)-2H-phthalazin-1-one,  
       (127) 4-(3-(5-(3-Methoxymethylpiperidin-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (128) 4-(3-(4-Dimethylaminobutyrylamino)-4-chlorophenyl)-2H-phthalazin-1-one,  
       (129) 4-(3-(4-Dimethylaminobutyrylamino)phenyl)-2H-phthalazin-1-one,  
       (130) 4-(4-Dimethylamino-3-(5-dimethylaminovalerylamino)phenyl)-2H-phthalazin-1-one,  
       (131) 4-(3-(5-Dimethylaminovalerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,  
       (132) 4-(3-(3-Morpholinopropylsulfonylamino)phenyl)-2H-phthalazin-1-one,  
       (133) 4-(3-(4-Morpholinobutylsulfonylamino)phenyl)-2H-phthalazin-1-one,  
       (134) 4-(3-(5-Morpholino-2,2-dimethylvalerylamino)phenyl)-2H-phthalazin-1-one,  
       (135) 4-(3-(4-Dimethylaminobutylsulfonylamino)phenyl)-2H-phthalazin-1-one,  
       (136) 4-(3-(4-Morpholinobutylsulfonylamino)-4-fluorophenyl)-2H-phthalazin-1-one,  
       (137) 4-(3-(4-(3-Methoxypiperidin-1-yl)butylsulfonylamino)phenyl)-2H-phthalazin-1-one,  
       (138) 4-(3-(5-(N-t-Butoxycarbonyl-N-ethylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (139) 4-(3-(5-(N-t-Butoxycarbonyl-N-propylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (140) 4-(3-(5-(N-Isopropyl-N-t-butoxycarbonylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (141) 4-(3-(7-t-Butoxycarbonylaminoheptanoylamino)phenyl)-2H-phthalazin-1-one,  
       (142) 4-(3-(2-(2-t-Butoxycarbonylaminoethyloxy)acetylamino)phenyl)-2H-phthalazin-1-one,  
       (143) 4-(3-(5-(N-Butyl-N-t-butoxycarbonylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (144) 4-(3-(5-t-Butoxycarbonylaminovalerylamino)-4-dipropylaminophenyl)-2H-phthalazin-1-one,  
       (145) 4-(3-(6-(N-Methyl-N-t-butoxycarbonylamino)hexanoylamino)phenyl)-2H-phthalazin-1-one,  
       (146) 4-(3-((3E)-5-t-Butoxycarbonylaminopentenoylamino)phenyl)-2H-phthalazin-1-one,  
       (147) 4-(3-(4-Amidinophenylcarbonylamino)phenyl)-2H-phthalazin-1-one,  
       (148) 4-(3-(2-(2-Dimethylaminoethylthio)acetylamino)phenyl)-2H-phthalazin-1-one,  
       (149) 4-(3-(4-Carbamoylbutyrylamino)phenyl)-2H-phthalazin-1-one,  
       (150) 4-(3-(4-(N-t-Butoxycarbonyl-N-methylamino)butyrylamino)phenyl)-2H-phthalazin-1-one,  
       (151) 4-(3-((2E)-5-t-Butoxycarbonylamino-2-pentenoylamino)phenyl)-2H-phthalazin-1-one,  
       (152) 4-(3-(3-(t-Butoxycarbonylamino)propionylamino)phenyl)-2H-phthalazin-1-one,  
       (153) 4-(3-(trans-2-Benzyloxycarbonylaminomethylcyclopropylcarbonylamino)phenyl)-2H-phthalazin-1-one,  
       (154) 4-(3-(2-(2-Morpholinoethylthio)acetylamino)phenyl)-2H-phthalazin-1-one,  
       (155) 4-(3-(2-(2-Morpholinoethyloxy)acetylamino)phenyl)-2H-phthalazin-1-one,  
       (156) 4-(3-(2-(2-Morpholinoethylthio)-2-methylpropionylamino)phenyl)-2H-phthalazin-1-one,  
       (157) 4-(3-(trans-2-Aminomethylcyclopropylcarbonylamino)phenyl)-2H-phthalazin-1-one,  
       (158) 4-(3-(5-(2-Methoxyethylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (159) 4-(3-(5-(N-2-Methoxyethyl-N-methylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (160) 4-(3-(5-(N-2-Hydroxyethyl-N-methylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (161) 4-(3-(5-t-Butoxycarbonylaminovalerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,  
       (162) 4-(3-(N-(5-t-Butoxycarbonylaminovaleryl)-N-methylamino)phenyl)-2H-phthalazin-1-one,  
       (163) 4-(3-(5-(2,3-Bis(t-butoxycarbonyl)guanidino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (164) 4-(3-(5-Ethylaminovalerylamino)phenyl)-2H-phthalazin-1-one,  
       (165) 4-(3-(5-Propylaminovalerylamino)phenyl)-2H-phthalazin-1-one,  
       (166) 4-(3-(5-Isopropylaminovalerylamino)phenyl)-2H-phthalazin-1-one,  
       (167) 4-(3-(7-Aminoheptanoylamino)phenyl)-2H-phthalazin-1-one,  
       (168) 4-(3-(2-(2-Aminoethyloxy)acetylamino)phenyl)-2H-phthalazin-1-one,  
       (169) 4-(3-(5-Butylaminovalerylamino)phenyl)-2H-phthalazin-1-one,  
       (170) 4-(3-(5-Aminovalerylamino)-4-dipropylaminophenyl)-2H-phthalazin-1-one,  
       (171) 4-(3-(6-Methylaminohexanoylamino)phenyl)-2H-phthalazin-1-one,  
       (172) 4-(3-((3E)-5-Amino-3-pentenoylamino)phenyl)-2H-phthalazin-1-one,  
       (173) 4-(3-(4-Methylaminobutyrylamino)phenyl)-2H-phthalazin-1-one,  
       (174) 4-(3-((2E)-5-Amino-2-pentenoylamino)phenyl)-2H-phthalazin-1-one,  
       (175) 4-(3-(5-Aminovalerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,  
       (176) 4-(3-(N-5-Aminovaleryl-N-methylamino)phenyl)-2H-phthalazin-1-one,  
       (177) 4-(3-(5-Guanidinovalerylamino)phenyl)-2H-phthalazin-1-one,  
       (178) 4-(3-(3-(2-Morpholinoethyl)-2-thioureido)phenyl)-2H-phthalazin-1-one,  
       (179) 4-(3-(3-(3-Morpholinopropyl)ureido)phenyl)-2H-phthalazin-1-one,  
       (180) 4-(3-(3-(3-Morpholinopropyl)-2-thioureido)phenyl)-2H-phthalazin-1-one,  
       (181) 4-(3-(2-Morpholinoethyloxycarbonylamino)phenyl)-2H-phthalazin-1-one,  
       (182) 4-(3-(2-(2-(Piperidin-1-yl)ethyloxy)acetyl)aminophenyl)-2H-phthalazin-1-one,  
       (183) 4-(3-(5-(4-Methoxypiperidin-1-yl)valerylamino-4-chlorophenyl)-2H-phthalazin-1-one, or  
       (184) 4-(3-(5-(4-Methoxypiperidin-1-yl)valerylamino-4-fluorophenyl)-2H-phthalazin-1-one,  
       or a non-toxic salt thereof. 
     
     
       8. A compound according to  claim 2 , which is 
       (1) 4-(3-(5-Bromovalerylamino)phenyl)-2H-phthalazin-1-one,  
       (2) 4-(3-(5-Bromovalerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,  
       (3) 4-(3-(5-Cyclohexylaminovalerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,  
       (4) 4-(3-(5-Cyclopentylaminovalerylamino)phenyl)-2H-phthalazin-1-one,  
       (5) 4-(3-(5-Cyclohexylaminovalerylamino)phenyl)-2H-phthalazin-1-one,  
       (6) 4-(3-(5-(N-Methyl-N-2-propynylamino)valerylaminomethyl)-2H-phthalazin-1-one,  
       (7) 4-(3-(5-(2,2,2-Trifluoroethylaminovalerylamino)phenyl)-2H-phthalazin-1-one,  
       (8) 4-(3-(5-Cyclopropylaminovalerylamino)phenyl)-2H-phthalazin-1-one,  
       (9) 4-(3-(5-(Cyclohexylmethylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (10) 4-(3-(5-(N,N-Bis(2-methoxyethyl)amino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (11) 4-(3-(5—Neopentylaminovalerylamino)phenyl)-2H-phthalazin-1-one,  
       (12) 4-(3-(5-(2-Propynylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (13) 4-(3-(5-Cyclopropylmethylaminovalerylamino)phenyl)-2H-phthalazin-1-one,  
       (14) 4-(3-(5-Cyclopentylmethylaminovalerylamino)phenyl)-2H-phthalazin-1-one,  
       (15) 4-(3-(5-Cyclobutylaminovalerylamino)phenyl)-2H-phthalazin-1-one,  
       (16) 4-(3-(5-(2-Fluoroethylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (17) 4-(3-(5-(2-Methyl-2-propenylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (18) 4-(3-(5-(2-(1-Cyclohexen-1-yl)ethylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (19) 4-(3-(5-(1,2-Dimethylpropylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (20) 4-(3-(5-Cyclopropylaminovalerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,  
       (21) 4-(3-(5-(2-Fluoroethylamino)valerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,  
       (22) 4-(3-(5-(2-Methyl-2-propenylamino)valerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,  
       (23) 4-(3-(5-(2-Propenylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (24) 4-(3-(5-(2-Propynylamino)valerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,  
       (25) 4-(3-(5-(2-Propenyloxyamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (26) 4-(3-(5-Cycloheptylaminovalerylamino)phenyl)-2H-phthalazin-1-one,  
       (27) 4-(3-(5-(2-Cyanoethylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (28) 4-(3-(5-Cyclobutylaminovalerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,  
       (29) 4-(3-(5-(2,6-Dimethylmorpholin-4-yl)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (30) 4-(3-(5-(2-Ethyl-4-methylimidazol-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (31) 4-(3-(5-Cyclopentylaminovalerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,  
       (32) 4-(3-(5-(2-Methylthioethylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (33) 4-(3(5-(N-Methyl-N-2-propynylamino)valerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,  
       (34) 4-(3-(5-(1-Methoxymethylcyclopentylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (35) 4-(3-(5-(Tetrahydropyran-4-ylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (36) 4-(3-(5-(2-Methoxycyclohexylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (37) 4-(3-(5-((1S, 2S)-2-Methoxycyclopentylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (38) 4-(3-(5-(2-Propenylamino)valerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,  
       (39) 4-(3(5-(2-Fluoroethylamino)valerylamino)-4-fluorophenyl)-2H-phthalazin-1-one,  
       (40) 4-(3-(5-(Tetrahydropyran-4-ylamino)valerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,  
       (41) 4-(3-(5-(3-Methylbutylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (42) 4-(3-(5-(N-Methyl-N-tetrahydropyran-4-yl)aminovalerylamino)phenyl)-2H-phthalazin-1-one,  
       (43) 4-(3-(5-(Piperidin-4-one-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (44) 4-(3-(5-((3R)-Tetrahydrofuran-3-ylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (45) 4-(3-(5-((3S)-Tetrahydrofuran-3-ylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (46) 4-(3-(4-Cyanobutyrylamino)-4-dimethylaminophenyl)-2H-phthalazin-1-one,  
       (47) 4-(3-(4-Cyanobutyrylamino)phenyl)-2H-phthalazin-1-one,  
       (48) 4-(3-(5-(N-3-Methyl-2-butenyl-N-t-butoxycarbonylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (49) 4-(3-(5-(N-2-Butynyl-N-t-butoxycarbonylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (50) 4-(3-(5-(N-Benzyloxycarbonyl-N-tetrahydrofuran-3-ylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (51) 4-(3-(5-(Tetrahydrofuran-3-ylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       (52) 4-(3-(5-(1,3-Dioxoisoindolin-2-yl)valerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,  
       (53) 4-(3-(5-(3-Methyl-2-butenylamino)valerylamino)phenyl)-2H-phthalazin-1-one, or  
       (54) 4-(3-(5-(2-Butynylamino)valerylamino)phenyl)-2H-phthalazin-1-one,  
       or a non-toxic salt thereof. 
     
     
       9. A compound according to  claim 2 , which is 
       (1) 4-(3-(5-Dimethylaminovalerylamino)-4-methoxyphenyl)-2H-phthalazin-1-one,  
       (2) 4-(3-(5-Dimethylaminovalerylamino)-4-hydroxyphenyl)-2H-phthalazin-1-one,  
       (3) 4-(3-(5-Dimethylaminovalerylamino)-4-methylphenyl)-2H-phthalazin-1-one,  
       (4) 4-(3-(5-Morpholinovalerylamino)-4-methylphenyl)-2H-phthalazin-1-one,  
       (5) 4-(3-(5-(3-Methoxypiperidin-1-yl)valerylamino)-4-methylphenyl)-2H-phthalazin-1-one,  
       (6) 4-(3-(4-Morpholinobutylsulfonylamino)-4-methoxyphenyl)-2H-phthalazin-1-one,  
       (7) 4-(3-(4-Morpholinobutylsulfonylamino)-4-methylphenyl)-2H-phthalazin-1-one, or  
       (8) 4-(3-(5-(4-Methoxypiperidin-1-yl)valerylamino-4-methylphenyl)-2H-phthalazin-1-one,  
       or a non-toxic salt thereof.